emd 525797 in combination with cetuximab and irinotecan in k-ras wild type metastatic colorectal cancer

Conditions: Metastatic Colorectal Cancer

Summary: the purpose of this study is to assess the safety and clinical activity of the experimental drug emd 525797 (study drug), a monoclonal antibody targeting alfa integrins, in combination with irinotecan and cetuximab in k-ras wildtype metastatic colorectal cancer patients.


Eligibility criteria:
inclusion criteria: subjects with histologically confirmed kras wildtype (wt) colorectal carcinoma (crc) with documented distant metastasis * prior oxaliplatin/fluoropyrimidine-containing regimen for the first-line treatment of metastatic disease * failed an oxaliplatin regimen for metastatic colorectal carcinoma (mcrc). failure is defined as either progressive disease (pd) (clinical or radiologic) within 6 months of the last dose of any agent of an oxaliplatin-based regimen or intolerance to an oxaliplatin regimen. intolerance to an oxaliplatin regimen is defined as discontinuation due to any of the following: severe allergic reaction, persistent severe neurotoxicity, or delayed recovery from toxicity preventing retreatment * at least 1 radiographically documented measurable lesion in a previously non irradiated area according to response evaluation criteria in solid tumors (recist, version 1.0), i.e., this lesion must be adequately measurable in at least 1 dimension (longest diameter to be recorded) as greater than or equal to (\>=) 2 centimeter (cm) by conventional techniques or \>=1 cm by spiral computed tomography (ct) scan * eastern cooperative oncology group (ecog) performance status 0 or 1, or karnofsky performance status (kps) \>= 80 percent (%) * absolute neutrophil count (anc) \>=1.5 x 10\^9/liter * platelets \>=100 x 10\^9/liter * hemoglobin \>=9 gram per deciliter (g/dl) (without transfusions) * bilirubin less than or equal to (\<=) 1.5 x upper limit normal (uln) * aspartate transaminase (ast) \<=5 x uln and alanine transaminase (alt) \<=5 x uln * serum creatinine \ =50 milliliter per minute (ml/min) * international nationalized ratio (inr), and partial thromboplastin time (ptt) within normal limits * sodium and potassium within normal limits or \<=10% above or below (supplementation permitted) exclusion criteria: * previous treatment with any inhibitor of epidermal growth factor receptor (egfr) * known brain metastasis and/or leptomeningeal disease * radiotherapy (except localized radiotherapy for pain relief), major surgery, or any investigational drug in the 30 days before the start of trial treatment entry; planned major surgery during the trial * concurrent chronic systemic immune or hormone therapy not indicated in this trial protocol (except for physiologic replacement; steroids up to 10 mg of prednisone equivalent or topical and inhaled steroids are allowed) * clinically relevant coronary artery disease (new york heart association \[nyha\] functional angina classification iii/iv), congestive heart failure (nyha iii/iv), clinically relevant cardiomyopathy, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia * uncontrolled hypertension defined as systolic blood pressure \>=160 millimeter of mercury (mmhg) and/or diastolic blood pressure \>=100 mmhg under resting conditions * history of coagulation disorder associated with bleeding or recurrent thrombotic events * history of recent peptic ulcer disease (endoscopically proven gastric, duodenal or esophageal ulcer) within 6 months of trial treatment start * chronic inflammatory bowel disease, or acute/chronic ileus * active infection (requiring i.v. antibiotics), including active tuberculosis, active or chronic hepatitis b or c, or ongoing hiv infection

Keywords: emd 525797 cetuximab irinotecan metastatic colorectal cancer